Cornea is a transparent avascular tissue having a diameter of about 1 cm and a thickness of about 1 mm, while conjunctiva is a mucosal membrane covering the eyeball surface posterior to the corneal margin, and the back face of the eyelid. The cornea and the conjunctiva are known to significantly affect the visual function. Keratoconjunctival disorders caused due to a variety of diseases such as corneal ulcer, keratitis, conjunctivitis, dry eyes and the like may adversely affect normal architecture of epithelium, and furthermore, may impair structures and functions of the stroma and endothelium, when the repair of these disorders are retarded, alternatively when these disorders are prolonged without making repair on some grounds. That is because the cornea and the conjunctiva are connected tissues. In these years, with the development of cell biology, factors participating in cell proliferation, migration, adhesion, extension, differentiation and the like had been elucidated, and it was reported that these factors play important roles in repair of corneal disorders (Japanese Review of Clinical Ophthalmology, 46, 738-743 (1992), Ophthalmic Surgery, 5, 719-727 (1992)).
JP-T-2002-515874 describes the invention which relates to a heterocyclic compound and discloses that an azolidinedione derivative such as 5-[4-[[3-methyl-4-oxo-3,4-dihydro-2-quinazolinyl]methoxy]phenylmethyl]thiazolidine-2,4-dione or a sodium salt thereof is effective as a therapeutic agent for a disease caused by insulin resistance such as type II diabetes or dyslipidemia, a cardiovascular disorders such as hypertension and a coronary heart disease. JP-T-2003-509503 describes the invention which relates to a substituted acid derivative which is useful as an anti-diabetes agent and an anti-obesity agent and discloses that a compound such as N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine is effective as a therapeutic agent for disease such as diabetes (particularly type II diabetes), hyperglycemia, hyperinsulinism, hyperlipemia or obesity. JP-A-2002-255854 describes the invention which relates to a pharmaceutical composition obtained by combining a diuretic and an insulin resistance improving agent and is characterized by suppressing an increase in heart weight, cardiac enlargement, the development of edema or fluid retention which is generally known as a side effect of an insulin resistance improving agent by the concomitant use of a diuretic, and discloses N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine as one of the insulin resistance improving agents.
However, there has been no report in which a pharmacological effect of these compounds on an eye disease such as a keratoconjunctival disorder is studied.